Chlamydia trachomatis is a major cause of sexually transmitted infections worldwide. Studies of ocular infections indicate that protective immunity is short-lived and serovar-specific. The chlamydial major outer membrane protein (MOMP) contains both serovar-specific and other epitopes of diverse specificities, which reside on 4 areas of MOMP termed variable sequence domains (VDs). Serovar-specific monoclonal antibodies are neutralizing in ocular and cell culture models. These data support the hypothesis that antibodies in serum or secretions directed to serotyping epitopes of MOMP are important in acquired immunity, but little is known about the human response to such epitopes. Repeated human genital infection, even with the same serovar, is common, but infection in exposed patients falls sharply with age, suggesting acquired immunity. The goal of this project is to examine the human antibody response in relation to age, and to recurrence or no recurrence on exposure. Immunoassays using synthetic peptides defining single MOMP epitopes implicated in the protective response will be developed for seroepidemiologic use. Since few MOMP epitopes have been mapped in genital strains, epitope mapping will be performed using anti-MOMP monoclonal antibodies to screen sets of overlapping synthetic peptides representing the 4 VDs of MOMP. Neutralization of chlamydial infection in cell culture by monoclonal antibodies will be used to select epitopes for further study. Mapped sequences relating to neutralizing antibodies will be used to produce synthetic peptides in quantity for adaptation to immunoassays to analyze human serum and secretions. The clinical base consists of banked sera, isolates and computer-accessible clinical data from over 600 patients with recurrences and 700 without recurrences previously identified by screening high risk patients in an STD clinic. This study will provide new data regarding the fine antigenic structure of the MOMPs of genital serovars and the molecular specificity of the human humoral immune response in genital infection as it relates to recurrence and age.